The role of the p75 neurotrophin receptor in the morphology of dorsal root ganglion cells in streptozotocin diabetic mice: effects of sciatic nerve crush

Abstract

Aims/hypothesis. Neuronal dorsal root ganglion (DRG) cells seem to be vulnerable in diabetes. The aim of this study was to determine whether the p75 neurotrophin receptor stimulates perikaryal shrinkage and neuronal death, and further accelerates neuronal DRG cell loss after axotomy in a mouse model of diabetes. Methods. Nine non-diabetic BALB/c p75 +/+ mice, seven diabetic BALB/c p75 +/+ mice, nine non-diabetic p75 −/− mice and nine diabetic p75 −/− mice received a unilateral sciatic nerve crush 1 to 2 days after streptozotocin treatment. Tissues were fixed 28 days later by vascular perfusion, and the volume and number of the fifth lumbar DRG neurons were obtained using assumption-free stereological techniques. Results. In diabetic p75 +/+ mice there was a 9% reduction in the perikaryal volume of the DRG A cells (p<0.05) and a 10% reduction in the perikaryal volume of the DRG B cells (p<0.05) on the non-crushed side compared with in non-diabetic p75 +/+ mice. However, neuronal cell number was not reduced. Conversely, no perikaryal shrinkage of A cells or B cells occurred on the non-crushed side in diabetic p75 −/− mice, and no neuronal cell loss was observed. Following nerve crush, there was a loss of B cells in non-diabetic p75 +/+ mice (37±6%) and in diabetic p75 +/+ mice (36±4%). In non-diabetic p75 −/− mice, no neuronal cell loss occurred after crush, whereas in diabetic p75 −/− mice the loss of B cells (14±4%) was small but significant (p<0.02). Conclusions/interpretation. In experimental diabetes the p75 neurotrophin receptor is involved in neuronal DRG cell body shrinkage without loss of neuronal DRG cells. Following sciatic nerve crush, DRG cell loss is not accelerated in diabetic p75 +/+ mice.

c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration

“…In the mutants, injured type B DRG neurons are about twice as likely to die as in WT mice. Even more notable is the death of about a third of type A neurons, because we find no death of these cells in WT animals, in agreement with previous work in mice and other species (Jiang and Jakobsen, 2004). The majority of facial motoneurons also die after facial nerve injury in the mutant (Fontana et al., 2012).…”

Diabetes does not accelerate neuronal loss following nerve injury

“…Studies on slow axonal transport in STZ diabetic rats showing that protein amount in the DRG and the transport rate are reduced as well as the significant perikaryal volume reduction of neuronal DRG. A cells and B cells in the present study indicate, however, that sensory neurons react to the diabetic condition and probably represent a changed balance between synthesis and axonal transport of structural proteins induced by p75 receptor activation ( Jiang and Jakobsen, 2004 ) .…”